The lifespan of thymic-derived or T lymphocytes is of particular interest because of their central role in immunological memory. Is the recall of a vaccination or early infection, which may be demonstrated clinically up to 50 years after antigen exposure, retained by a long-lived cell, or by its progeny? Using the observation that T lymphocyte expression of isoforms of CD45 corresponds with their ability to respond to recall antigens, we have investigated the lifespan of both CD45R0 (the subset containing responders, or 'memory' cells) and CD45RA (the unresponsive, or 'naive' subset) lymphocytes in a group of patients after radiotherapy. Here we report rapid loss of unstable chromosomes from the CD45R0 but not the CD45RA pool. Immunological memory therefore apparently resides in a population with a more rapid rate of division. Differing survival curves for the two subsets are best described by a model in which there is also reversion in vivo from the CD45R0 to the CD45RA phenotype. Expression of CD45R0 in T cells may therefore be reversible.

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Kawasaki disease is a systemic vasculitis of unknown etiology, with clinical observations suggesting a substantial genetic contribution to disease susceptibility. We conducted a genome-wide association study and replication analysis in 2,173 individuals with Kawasaki disease and 9,383 controls from five independent sample collections. Two loci exceeded the formal threshold for genome-wide significance. The first locus is a functional polymorphism in the IgG receptor gene FCGR2A (encoding an H131R substitution) (rs1801274; P = 7.35 × 10(-11), odds ratio (OR) = 1.32), with the A allele (coding for histadine) conferring elevated disease risk. The second locus is at 19q13, (P = 2.51 × 10(-9), OR = 1.42 for the rs2233152 SNP near MIA and RAB4B; P = 1.68 × 10(-12), OR = 1.52 for rs28493229 in ITPKC), which confirms previous findings(1). The involvement of the FCGR2A locus may have implications for understanding immune activation in Kawasaki disease pathogenesis and the mechanism of response to intravenous immunoglobulin, the only proven therapy for this disease.

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We present data on the decay, after radiotherapy, of naive and memory human T lymphocytes with stable chromosome damage. These data are analyzed in conjunction with existing data on the decay of naive and memory T lymphocytes with unstable chromosome damage and older data on unsorted lymphocytes. The We use two data sets from which to estimate life-history parameters of human T lymphocytes in vivo. Both come from cross-sectional studies of the number of lymphocytes with radiation-induced chromosomal damage. The data of Buckton et at (6) record the proportion of lymphocytes with stable and unstable damage in men given radiation therapy as treatment for ankylosing spondylitis. The data of Michie (7) record the proportion of T lymphocytes of primed and unprimed subsets with stable and unstable damage. By using these two data sets, we are able to estimate death rates, proliferation rates, and interconversion rates for primed and unprimed T lymphocytes. We then use these rate estimates as parameters for a simple mathematical model of the population dynamics of peripheral T cells. Investigation of the behavior of this simple model allows us to make some inferences about the broader implications of the data. METHODSBuckton's Data. Full details concerning the methods for collecting these data are given in the original paper (6). We give a brief summary. One hundred and twenty-nine venous blood samples were taken from 66 men between 0 and 3700 days after they had received x-ray treatment for ankylosing spondylitis. Chromosome preparations were made from lymphocytes and classified into groups by the method of Buckton and Pike (4). Data were then aggregated into 14 groups of 8-12 observations. Only the aggregated data were reported and it is these aggregated data that we use. Although Buckton's samples must have contained small numbers of B cells, we assume that they are present in such small proportions that we can ignore them. We therefore treat Buckton's data (6)

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The UK and Ireland incidence of KD has increased and is more frequently seen in winter and rural areas. Delayed IVIG treatment is associated with CAA, suggesting earlier and adjunctive primary treatment might reduce complications to prevent CAA, particularly in the very young.

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